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Mol Ther Methods Clin Dev. 2014 Jun 25;1:14024. doi: 10.1038/mtm.2014.24. eCollection 2014.

Maintaining therapeutic activity in the operating room: compatibility of a gamma-retroviral replicating vector with clinical materials and biofluids.

Molecular therapy. Methods & clinical development

Ryan Burnett, Carlos E Ibañez, Pär L Pettersson, Ching-I Chen, Shraddha Parab, Tiffany Huang, Joan Robbins, Krystof Bankiewicz, Manish Aghi, Christopher Logg, Noriyuki Kasahara, Dan Pertschuk, Harry E Gruber, Douglas J Jolly

Affiliations

  1. Tocagen Inc., Bunker Hill St. , San Diego, CA, USA.
  2. Department of Neurological Surgery, University of California San Francisco (UCSF) , San Francisco, CA, USA.
  3. Department of Medicine, University of California Los Angeles (UCLA) , Los Angeles, CA, USA.

PMID: 26015967 PMCID: PMC4362351 DOI: 10.1038/mtm.2014.24

Abstract

Toca 511 is a novel retroviral replicating vector, encoding a modified yeast cytosine deaminase, administered to recurrent high grade glioma patients in Phase 1 trials by stereotactic, transcranial injection into the tumor or into the walls of the resection cavity. A key issue, with little published data, is vector biocompatibility with agents likely to be encountered in a neurosurgical setting. We tested biocompatibility of Toca 511 with: delivery devices; MRI contrast agents, including ProHance supporting coinjection for real time MRI-guided intratumoral delivery; hemostatic agents; biofluids (blood and cerebrospinal fluid); potential adjuvants; and a needleless vial adapter that reduces risk of accidental needle sticks. Toca 511 is stable upon thawing at ambient temperature for at least 6 hours, allowing sufficient time for administration, and its viability is not reduced in the presence of: stainless steel and silica-based delivery devices; the potential MRI contrast agent, Feraheme; ProHance at several concentrations; the hemostatic agent SURGIFOAM; blood; cerebrospinal fluid; and the needleless vial adapter. Toca 511 is not compatible with the hemostatic agent SURGICEL or with extended exposures to titanium-based biopsy needles.

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